Breaking News
April 21, 2018 - Americans world’s biggest TV addicts, watching four hours a day
April 21, 2018 - Investigational drug may help increase protein levels in babies with spinal muscular atrophy
April 21, 2018 - Study shows distinctions between age groups in predicting and responding to stress at home
April 21, 2018 - Aziyo Biologics, BIOTRONIK enter into US co-distribution agreement
April 21, 2018 - Opiate Use Linked to Early Mortality in IBD Patients
April 21, 2018 - Online ads help pregnant smokers quit
April 21, 2018 - Opioid pain medications may not be safe for hemodialysis patients
April 21, 2018 - Rare variants in non-coding DNA inherited from parents heighten autism risk
April 21, 2018 - A needleless glucose monitor for diabetes patients
April 21, 2018 - BD introduces new informatics and automation solutions for clinical laboratories
April 21, 2018 - Turn Chores Into a Fitness Routine
April 21, 2018 - DNA methylation plays key role in stem cell differentiation
April 21, 2018 - Scientists find link between soil metals and cancer mortality
April 21, 2018 - Experts discuss implications of low calcium intake in global population
April 21, 2018 - GNA Biosolutions to display Pharos V8 Laser PCR instrument at Analytica trade fair
April 21, 2018 - People with vitamin D deficiency may be at greater risk of diabetes
April 21, 2018 - Study findings could open new possibilities for treating cancer with adenovirus
April 21, 2018 - People who use medical marijuana have higher rates of prescription drug use, study finds
April 21, 2018 - Study debunks ‘myth’ that strenuous exercise dampens immunity
April 21, 2018 - FDA approves marijuana based medication for epilepsy treatment
April 21, 2018 - Researchers find novel genes for longevity in mammals
April 21, 2018 - GNA Biosolutions and project partners launch new research project to develop TB diagnostic platform for POC applications
April 21, 2018 - Scientists identify gene responsible for evolution of recombination rates
April 21, 2018 - UConn researchers develop new composite for healing broken load-bearing bones
April 21, 2018 - Study challenges use of whole-brain radiation for small-cell lung cancer patients with brain metastases
April 21, 2018 - People who become physically active after heart attack more likely to live longer, shows research
April 21, 2018 - CPRIT awards $2 million grant to push forward breast cancer research in West Texas
April 21, 2018 - Unhealthy diet damages the development of immature fat cells, study shows
April 21, 2018 - Consumption of protein supplements with meals may provide better weight control
April 21, 2018 - 4 Types of Foods to Help Boost Your Memory
April 21, 2018 - How did gonorrhea become a drug-resistant superbug?
April 21, 2018 - DePuy Synthes announces clinical results related to use of CORAIL Hip System Femoral Stems
April 21, 2018 - New initiative launched to support goals of Human Cell Atlas
April 20, 2018 - Teen patient gets a new lease on life
April 20, 2018 - Cancer Australia launches new framework to improve outcomes for lung cancer patients
April 20, 2018 - ‘Gut-on-a-chip’ model recreates intestinal matrix critical for nutrient absorption
April 20, 2018 - Researchers develop new drug-testing platform for epilepsy
April 20, 2018 - FDA Alert: NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall
April 20, 2018 - Pelizaeus-Merzbacher-like disease type 1 – Genetics Home Reference
April 20, 2018 - Tick-borne diseases reach epidemic levels, panel says
April 20, 2018 - A potential “male pill” without side effects
April 20, 2018 - Researchers discover new information related to rare form of leukemia
April 20, 2018 - Researchers find crucial links between dopamine and avoidance behavior
April 20, 2018 - UGA scientist creates system for efficient detection of foodborne pathogens
April 20, 2018 - Social Support of Autonomy Tied to Better Glycemic Control in DM
April 20, 2018 - Study reports use of nutritional ketosis with mobile app intervention could reverse Type 2 diabetes
April 20, 2018 - New microscopy techniques allow quasi-biochemical studies on living T cells
April 20, 2018 - Study shows connection between muscular strength and brain health
April 20, 2018 - Ecolab introduces Life Sciences cleanroom program in North America
April 20, 2018 - Normal weight people with fat belly may have more chance of heart problems
April 20, 2018 - Male fruit flies like sex and alcohol
April 20, 2018 - Meditation could help reduce anxiety levels and some heart health risk factors
April 20, 2018 - Improving job prospects unlikely to control opioid epidemic
April 20, 2018 - Skin Sensor Might Someday Track Alcoholics’ Booze Intake
April 20, 2018 - The relevance of GABA for diabetes highlighted in two new studies
April 20, 2018 - Novel method enables fast and noninvasive assessment of tumor status
April 20, 2018 - IU psychologist receives NIH grant to study earliest phases of language learning in children
April 20, 2018 - Walking fast lowers risk of hospitalization in heart patients, shows study
April 20, 2018 - Study reveals surprising insights into RNA-binding proteins
April 20, 2018 - Young victims of cyberbullying twice as likely to attempt suicide and enact suicidal behavior
April 20, 2018 - Role of UBE3A enzyme in Angelman syndrome
April 20, 2018 - NovaDigm Therapeutics initiates NDV-3A Phase 2a study for reduction of S. aureus in military trainees
April 20, 2018 - High-tech microscope reveals how cancer-causing virus anchors itself to human DNA
April 20, 2018 - Experimental compound reduces destructive inflammation to improve stroke outcome
April 20, 2018 - The May issue of Drug Discovery Today is a Special Issue and will be published very soon
April 20, 2018 - Larger families linked to heightened tooth loss risk for moms
April 20, 2018 - Scientists develop tiny fluorescent probe that seeks out GLUT5 and detects cancer cells
April 20, 2018 - The Swedish Childhood Cancer Foundation awards grant to KI researchers
April 20, 2018 - AMSBIO’s MC-Easy minicircle technology allows sustained transgene expression in quiescent cells and tissues
April 20, 2018 - Researchers use optogenetics to treat chronic pain
April 20, 2018 - Discovery of 100 new genes may aid research into pigmentation
April 20, 2018 - AYOXXA introduces new LUNARIS Mouse 12-Plex Th17 Kit for quantitative analysis of Th17 cell biology
April 20, 2018 - Compound derived from immune cells treats psoriasis in mice
April 20, 2018 - GABA-transaminase deficiency – Genetics Home Reference
April 20, 2018 - Key heart risks decline for older Americans
April 20, 2018 - UD professor wins $2.3 million grant from NIH for research on Achilles tendinopathy
April 20, 2018 - Researchers discover unique protein in malaria parasite that could be new drug target
April 20, 2018 - Bio-Techne expands automation capabilities of popular RNAscope ISH technology
April 20, 2018 - Smartphone app effective in promoting proper child car seat practices
April 20, 2018 - Nutraceuticals could play an important role in preventing heart disease
Researchers discover ‘missing mutation’ in severe infant epilepsy

Researchers discover ‘missing mutation’ in severe infant epilepsy

image_pdfDownload PDFimage_print

Researchers have discovered a “missing mutation” in severe infant epilepsy–long-suspected genetic changes that might trigger overactive, brain-damaging electrical signaling leading to seizures. They also found early indications that specific anti-seizure medications might prevent disabling brain injury by controlling epilepsy during a crucial period shortly after birth.

“These are still early days, but we may be able to use this knowledge to protect the newborn brain and improve a child’s long-term outcome,” said study leader Ethan M. Goldberg, MD, PhD, a pediatric neurologist at Children’s Hospital of Philadelphia.

Goldberg collaborated with European and American researchers in this neurogenetic study of early infantile epileptic encephalopathy, published online Feb. 21, 2018 in Annals of Neurology.

The study focused on mutations in the gene SCN3A. Scientists already knew that the gene had a pattern of high expression in the brain, before and shortly after birth. Variants in SCN3A had also been previously linked to less severe forms of epilepsy, but the current research solidified this link and was the first to establish that SCN3A mutations cause the severe infantile form.

The gene regulates sodium channels that allow sodium ions into brain cells: “sodium influx underlies action potentials, which are the currency of information transfer in the brain,” said Goldberg. Of four sodium ion channels predominantly expressed in the brain, he added, scientists had discovered that gene mutations in three of those channels already had a clear role in causing forms of epilepsy. Only one channel, called Nav1.3, encoded by the SCN3A gene, had not previously been linked to epilepsy, and hence was the “missing channel.” The new research implicated novel SCN3A mutations in severe childhood epilepsy, joining the other brain-expressed sodium channels as causes of early infantile epileptic encephalopathy.

“We identified gain-of-function mutations in SCN3A,” said Goldberg. “These mutations generate increased channel activity that leaves the ion channel stuck open and leaking current. This overactivity, in turn, leads to epileptic encephalopathy–the most severe type of childhood epilepsy.”

The study team reported on a cohort of four unrelated children from different countries, all of whom had severe epilepsy. Their epilepsy had a particularly early onset, within the first two weeks of life. For the children, the results were devastating: severe to profound developmental delay, seizures that did not respond to medication and lifelong disability.

The researchers used whole-exome sequencing to pinpoint mutations in SCN3A. The mutations were de novo–present in the affected children, but not inherited from the parents. Cell studies, including electrophysiological recordings, revealed detailed properties of the electrical signaling.

Further cell culture studies also showed that existing anti-seizure medications, lacosamide and phenytoin, selectively inhibited the persistent current in mutant ion channels–suggesting a possible future therapy for this condition.

Translating these findings into potential clinical treatments, Goldberg stressed, will require considerable further research–both in nerve cells and in future animal models, in which neurologists can test possible precision-medicine treatments for safety and efficacy before they can be investigated in patients. In addition, the current research allowed the SCN3A gene to be added to an existing diagnostic test, CHOP’s Epilepsy Panel, which uses next-generation sequencing to rapidly test for over 100 genetic causes of childhood epilepsy.

Precise, early diagnosis, added Goldberg, will be crucial, because of the highly regulated timetable of early-life neurological events. “The mutation’s activity in the Nav1.3 sodium ion channel occurs during a short period in newborns, but if we can intervene during that window, we may be able to help prevent long-term neurological injury and benefit patients,” he said.

Tagged with:

About author

Related Articles